title: Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo.
abstract: The mitotic spindle checkpoint is a key signaling pathway that ensures proper chromosome segregation and was suggested as a novel target for anti-cancer treatment. Here, we explore a nanoparticle-based RNAi approach targeting the key spindle checkpoint gene MAD2 to investigate the suitability of the spindle checkpoint as a therapeutic target in vitro and in vivo. Repression of MAD2 causes severe chromosome missegregation in colon carcinoma cells associated with induction of apoptosis. Systemic administration of siRNA nanoparticles in nude mice results in reduced growth of xenograft tumors suggesting that inhibition of the spindle checkpoint represents a promising new concept for cancer therapy.
authors.affiliation: Georg-August University Göttingen, University Medical Center, Department of Molecular Oncology, Germany.
authors.forename: Phillip
authors.initials: P
authors.lastname: Kaestner
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
authors.forename: Holger
authors.initials: H
authors.lastname: Bastians
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002469:Cell Separation; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D064246:Mad2 Proteins; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy*; D011094:Polyethyleneimine / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D012097:Repressor Proteins / Q000235:genetics*; D008941:Spindle Apparatus / Q000235:genetics / Q000473:pathology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D011094:Polyethyleneimine